Proton pump inhibitor is a drug that acts on proton pumps in parietal cells in stomach, and inhibits secretion of gastric acid. Proton pump inhibitor is useful for treating gastric ulcer, duodenal ulcer, anastomotic ulcer, reflux esophagitis, non-erosive gastroesophageal reflux disease or Zollinger-Ellison syndrome, and for sterilization supplement for Helicobacter pylori in gastric ulcer, duodenal ulcer, gastric MALT lymphoma, idiopathic thrombocytopenic purpura, remnant stomach after endoscopic submucosal dissection for early gastric cancer, or Helicobacter pylori gastritis, and the like. As a proton pump inhibitor compound, a benzimidazole-type or imidazopyridine-type compound or the like are known, as represented by, for example, omeprazole, esomeprazole, lansoprazole, rabeprazole, tenatoprazole, pantoprazole, reminoprazole, dexlansoprazole, which are shown below. The terms “proton pump inhibitor compound” and “benzimidazole-type or imidazopyridine-type compound” as used herein, include either a neutral form or a salt form, or both forms.

The proton pump inhibitor compound may exist as S-form, R-form or a racemate, based on the conformational structure of the sulfur atom in the sulfoxide, as a common characteristic of their structure. As for omeprazole, its racemate is called omeprazole, and its S-form is called esomeprazole, both of which are commercially available. Esomeprazole has smaller inter-individual variation in pharmacokinetics and pharmacodynamic effects as compared with omeprazole, and was developed as a drug that exerts more clinical effects beyond omeprazole. Thus, since an optically active proton pump inhibitor compound was expected to have better clinical effects than its racemic form, a method of producing its optically active compound efficiently had been desired.
Patent Literature 1 discloses a method of producing esomeprazole by preparing an ester of a racemic omeprazole with an optically active acid, followed by separating the obtained diastereomers. However, the method requires multi-steps, and the other optical isomer is discarded. Therefore, this method is not preferable.
Non-Patent Literature 1 and Patent Literature 2 disclose a method of producing optically active esomeprazole by asymmetric oxidation. The authors reported that enantioselectivity of 94% ee or more was obtained by this method using titanium as a catalyst, and diethyl (S, S)-tartrate as a chiral ligand, and cumene hydroperoxide as an oxidant. However, they describe that the asymmetric oxidation reaction using this titanium catalyst was not reproducible. Particularly, while asymmetric oxidation using a catalyst amount of 4 mol % proceeded with 91% ee on a small scale, this results could not be reproduced with the same catalyst amount on a larger scale, and a catalyst amount of for example 30 mol % was required for asymmetric oxidation. Accordingly, the method of Non-Patent Literature 1 and Patent Literature 2 have problems that a large amount of the catalyst and the chiral ligand are necessary on an industrial scale, and furthermore, these catalysts, chiral ligands and oxidants are expensive and not easy to handle.
Patent Literatures 3 and 4 disclose examples in which the method of Non-Patent Literature 1 was applied to other proton pump inhibitor compounds such as lansoprazole and the like. Patent Literature 5 discloses a method of producing esomeprazole using optically active methyl mandelate instead of a tartarate derivative in the method of Non-Patent Literature 1. In the methods of Patent Literatures 3 to 5, a large amount of titanium catalyst is used as in the method of Non-Patent Literature 1.
Patent Literature 6 discloses a method of producing an optically active form of pantoprazole and the like, using zirconium or hafnium instead of titanium catalyst in the method of Non-Patent Literature 1. However, the method has problems that the catalysts, chiral ligands and oxidants are expensive and not easy to handle.
Patent Literature 7 discloses a method of producing an optically active form of tenatoprazole using tungsten or vanadium as a catalyst, an alkaloid derivative or an imine derivative as a chiral ligand and hydrogen peroxide as an oxidant. It describes for example, in Example 1, that the desired optical isomer was obtained in 70% yield and 90% ee, after the reaction, extraction and concentration under a reduced pressure. However, the contents of the sulfone compound and the unreacted sulfide compound are not described, which should also be present after only simple extraction. Moreover, the yield of the compound obtained after recrystallization is not described at all. Therefore, the above yield is considered to be a numerical value including impurities which is unreliable and the yield is not considered to be so high. Furthermore, the method of Patent Literature 7 has problems that these catalysts and chiral ligands are expensive and not easy to handle as in Patent Literature 6.
Non-Patent Literature 2 discloses that an optically active form of lansoprazole was produced using a tungsten catalyst, an alkaloid derivative as a chiral ligand, and hydrogen peroxide as an oxidant. However, the method has problems that the catalysts and chiral ligands are expensive and not easy to handle.
Patent Literature 8 discloses a method of producing esomeprazole using a manganese salt as a catalyst, salen derivative as a chiral ligand and hydrogen peroxide as an oxidant. However, the yield is 6 to 62% and the enantioselectivity is 3 to 62% ee, which are not satisfactory for a method of producing an optically active compound. Furthermore, when manganese was replaced by iron as described in Example 37, the yield decreased to 17% and the enantioselectivity to 18% ee. A person skilled in the art who reads Patent Literature 8 would understand that iron is inferior to manganese as a catalyst and is not a preferable catalyst in the production of proton pump inhibitors having similar benzimidazole-type and imidazopyridine-type structure including esomeprazole.
A method of asymmetric oxidation of a sulfide using an iron catalyst is described in Non-Patent Literatures 3 and 4. This method uses a specific imine compound as a chiral ligand, iron (III) acetylacetonate as an iron salt, and hydrogen peroxide in water as an oxidant. As shown in Table 3 of Non-Patent Literature 4, the yield is 36 to 78% and the enantioselectivity is 23 to 96% ee when additives were used. From the results, it seems that the yield and enantioselectivity are largely dependent on the structure of the starting material sulfide. Also, the sulfides used are mainly limited to those having an aromatic hydrocarbon group and an alkyl group. Therefore, it is impossible for a person skilled in the art to predict the yield and enantioselectivity for the asymmetrical oxidation of a compound having a heterocyclic ring under these conditions.